The effects of vitamin K-antagonists on survival of patients with malignancy: a systematic analysis.
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Adenocarcinoma↗
Biomedical subjects
R Vink
Publications and source records attributed to R Vink.
Regulation of intracellular free magnesium in central nervous system injury.
Traumatic injury to the central nervous system (CNS) initiates an autodestructive cascade of biochemical and pathophysiological changes that ultimately results in irreversible tissue damage. Known as secondary injury, this delayed injury process is multifactorial in nature and it is generally thought that the simultaneous attenuation of a number of the secondary injury factors will be required for interventional therapies to have a significant beneficial effect on outcome. This review summarizes the growing body of evidence that suggests that magnesium plays a pivotal role in the secondary injury process following CNS trauma, affecting a number of secondary injury factors including neurotransmitter release and activity, ion changes, oxidative stress, protein synthesis, and energy metabolism. By having effects on such a range of secondary injury factors following trauma, pharmacological studies have shown that magnesium may be an effective therapy following neurotrauma, improving survival, motor outcome and alleviating cognitive deficits.
Animals↗
Hepatocellular carcinoma in glycogen storage disease type IV.
A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.
Adolescent↗
Translocations (X;10)(p22;q24) and (1;10)(q21;q11) in a follicular adenoma of the thyroid without apparent involvement of the RET protooncogene.
We report here the cytogenetic analysis of a follicular adenoma of the thyroid which revealed an abnormal clone with a t(X;10)(p22;q24) and a t(1;10)(q21;q11) together with normal cells. Fluorescence in situ hybridization (FISH) with YACs 273E3 and 344H4, which are located on 10q11.2 and are specific for the RET protooncogene, showed no abnormalities. It would therefore appear that this gene is not involved in the particular tumor, as has been reported in a number of papillary thyroid carcinomas. Several chromosomal aberrations have been suggested as been specific for follicular thyroid adenoma. However, until now, only a few such cases have been reported which involve structural abnormalities of chromosomes 10q11.2 and 10q24. We believe this to be the first report of a follicular thyroid adenoma with a t(X;10)and a t(1;10).
Adenoma↗
In vivo treatment of rats with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) does not affect experimentally induced colon carcinoma metastasis.
Recent randomized trials have suggested that treatment with low molecular weight heparin (LMWH) improves survival of cancer patients with venous thromboembolism, as compared to treatment with unfractionated heparin (UFH). Experimental studies have shown that UFH has activities besides its anticoagulant function which may affect progression of malignancy, including stimulation of new blood vessel formation. In contrast, LMWH has been suggested to inhibit angiogenesis. In the present study, we compared quantitatively the effects of treatment with UFH, LMWH or placebo on the development of experimentally induced colon carcinoma metastases in rat liver and on tumor-associated angiogenesis. It is shown that UFH and LMWH in therapeutic dosages neither affect development of metastases nor tumor blood vessel formation in this animal model. These results indicate that heparins do not affect colon cancer metastasis in liver. Further studies in other animal models are required to establish the mechanisms by which heparins potentially affect cancer.
Animals↗
Secondary mechanisms in traumatic brain injury: a nurse's perspective.
Effective management of brain-injured patients requires that nurses have a specialized body of knowledge relating to the pathophysiology and treatment of traumatic brain injury (TBI). Current research in this area has focused on the cascade of secondary injury which leads to the irreversible tissue damage following TBI. Such processes involve excitatory amino acids, neurotransmitters, ion changes, lipid peroxidation, oxygen free radicals, opioids, lactic acidosis and magnesium to name but a few. Given that no accepted treatment paradigm exists to attenuate these secondary processes, nurses may have to autonomously devise individual care plans based on their current understanding of brain injury pathophysiology.
Brain Injuries↗
Colitis may be part of the antiepileptic drug hypersensitivity syndrome.
PURPOSE: To show that colitis may be part of the antiepileptic hypersensitivity syndrome. METHODS: Description of two case histories. RESULTS: The first patient was a 47-year-old man who developed fever, lymphadenopathy, influenza-like symptoms, facial edema, skin rash and diarrhea after 3 weeks of carbamazepine (CBZ) treatment. Laparotomy because of severe abdominal pain 2 weeks later showed severe colitis with perforations. The second patient was a 41-year-old woman who developed fever, diarrhea, and skin rash 4 weeks after start of CBZ treatment. A colon biopsy confirmed colitis. Stool examinations did not show pathogenic microorganisms, and there was no evidence of Crohn's disease or ulcerative colitis. Both patients had elevated liver enzymes, peripheral eosinophilia, and eosinophils in the infiltrate of the colon. CONCLUSIONS: In view of the close temporal relation between start of CBZ intake and development of colitis, the presence of fever, lymphadenopathy, and rash, and improvement after discontinuation of CBZ, we conclude that the two patients developed an AED hypersensitivity syndrome. Our case histories demonstrate that severe colitis may be part of this syndrome.
Adult↗
Gestational magnesium deficiency is deleterious to fetal outcome.
A number of recent epidemiological findings have implicated magnesium as being essential to fetal well-being. Few studies, however, have examined the relationship between maternal requirements for dietary magnesium and subsequent mortality and morbidity in offspring. The present study uses a rodent model of dietary-induced hypomagnesemia to investigate the effects of magnesium deficiency prior to and during gestation on neonatal morbidity and mortality. Magnesium deficiency during gestation significantly increased neonatal mortality and morbidity. Such increases were associated with a reduced free magnesium concentration in both maternal and offspring blood and an increased incidence of periventricular hemorrhage and edema in newborn pups as observed by magnetic resonance imaging and histology. Animals fed a magnesium-deficient diet before mating but given magnesium supplementation during gestation did not demonstrate a significant change in neonatal mortality and morbidity when compared to control animals. The significant improvement in fetal outcome with dietary magnesium supports the concept of magnesium supplementation during pregnancy.
Animals↗
Improved motor outcome in response to magnesium therapy received up to 24 hours after traumatic diffuse axonal brain injury in rats.
OBJECT: The goal of this study was to establish the therapeutic window during which delayed therapy with MgSO4 improves neurological motor outcome in rats that have suffered severe traumatic axonal brain injury. METHODS: Severe brain injury was induced in male Sprague-Dawley rats by using the impact-acceleration model of severe traumatic diffuse axonal brain injury. Injured animals were subsequently treated with MgSO4 (750 micromol/kg) infused intramuscularly at 30 minutes or at 8, 12, or 24 hours after trauma and were tested for neurological motor outcome during the following week by using the rotarod test. Injured untreated (control) animals demonstrated highly significant (p < 0.001) neurological motor deficits that were sustained over the 1-week assessment period. Animals treated with MgSO4 at 30 minutes or at 8 or 12 hours postinjury demonstrated significantly improved motor outcomes compared with untreated control animals at all time points (0.001 < p < 0.05). Animals treated with MgSO4 at 24 hours had motor scores that were similar to those of untreated control animals early in the week, but demonstrated a significantly more rapid recovery in function and, by the end of the assessment period, they demonstrated significantly improved motor scores (p < 0.01). Repeated administration of MgSO4 over the 1-week observation period did not further improve outcome. CONCLUSIONS: The present results demonstrate that Mg++ plays a neuroprotective role following severe diffuse traumatic axonal brain injury. Moreover, Mg++ therapy significantly improved motor outcome when administered up to 24 hours after injury, with early treatments providing the most significant benefit. Repeated administration beyond 24 hours postinjury did not provide additional neuroprotection.
Animals↗
Optimization of magnesium therapy after severe diffuse axonal brain injury in rats.
A number of studies have demonstrated that magnesium salts given after traumatic brain injury improve subsequent neurologic outcome. However, given that these earlier studies have used a number of different salts, dosages, and routes of administration, follow-up studies of the neuroprotective properties of magnesium are complicated, with comparisons to the earlier literature virtually impossible. The present study has therefore characterized the dose-response characteristics of the most commonly used sulfate and chloride salts of magnesium in a severe model of diffuse traumatic axonal injury in rats. Both magnesium salts improved neurologic outcome in rats when administered as a bolus at 30 min after injury. The i.v. and i.m. optima of each salt was 250 micromol/kg and 750 micromol/kg, respectively. The identical concentrations required for improved neurologic outcome suggest that improvement in outcome was dependent on the magnesium cation and not the associated anion. Subsequent magnetic resonance studies demonstrated that the administered magnesium penetrated the blood-brain barrier after injury and resulted in an increased brain intracellular free magnesium concentration and associated bioenergetic state as reflected in the cytosolic phosphorylation potential. Both of these metabolic parameters positively correlated with resultant neurologic outcome measured daily in the same animals immediately before the magnetic resonance determinations.
Animals↗
Brain free magnesium concentration is predictive of motor outcome following traumatic axonal brain injury in rats.
A number of studies have supported a role for brain free magnesium as an important secondary injury factor in the development of neurologic deficits following traumatic brain injury. Despite this, few studies have characterised free magnesium changes in diffuse models of brain injury relevant to clinical trauma, and none have critically examined the association between brain free magnesium concentration and degree of neurologic deficit following graded trauma. In the present study, a combination of nuclear magnetic resonance spectroscopy and rotarod motor function tests were used to characterise the relationship between brain free magnesium concentration and neurologic motor function following graded traumatic axonal brain injury in rats. Induction of moderate or severe impact-acceleration induced traumatic brain injury resulted in a profound decline (p < 0.01) in brain free magnesium concentration that persisted for a minimum of 4 days post-trauma in both injury groups. Posttraumatic rotarod deficits assessed on a daily basis after injury were linearly correlated with brain free magnesium concentration measured in the same animals immediately after the motor tests were performed (r = 0.87; p < 0.001). These results suggest that brain free magnesium declines following graded diffuse axonal brain injury and that the concentration of the ion after trauma may be a prognostic indicator of motor outcome following.
Animals↗
The effects of unfractionated heparin on survival in patients with malignancy--a systematic review.
Clinical and experimental studies have suggested that unfractionated heparin (UFH) effects malignancy progression. We reviewed all published clinical reports concerning the effects of UFH, as compared to no treatment on survival of cancer patients. Studies were classified on methodological strength and subdivided as to whether therapeutic or prophylactic dosages of UFH were used. Mortality rates after 3 years were extracted or calculated. One randomized study that evaluated the use of UFH in therapeutic dosages in patients with small cell lung carcinoma reported on an improved survival (odds ratio (OR) 0.64; 95% confidence interval (CI): 0.25 to 1.62). A detrimental effect was observed in 2 randomized studies which investigated the effects of intraportal UFH treatment in a prophylactic dose after surgery for gastrointestinal cancer (OR 1.66; 95% CI: 1.02 to 2.71). In contrast, level 2 studies in which either therapeutic or prophylactic dosages of UFH on mortality of patients with gastrointestinal cancer were evaluated, showed OR of 0.58 (95% CI; 0.11-3.13) and 0.65 (95% CI 0.51 to 0.84), respectively. We conclude that there is no convincing evidence of either positively or negatively effects of UFH on survival of patients with malignancy.
Humans↗
Blood-free magnesium concentration declines following graded experimental traumatic brain injury.
Traumatic brain injury has been shown to result in a decrease in brain-free magnesium concentration that is associated with the development of neurologic motor deficits. Although these changes have been well characterized in the brain, changes in free magnesium homeostasis have not been characterized in other fluid compartments. The current experiments use ion selective electrodes to measure alterations in blood-free magnesium concentration following graded experimental brain injury in rats and to compare these changes with subsequent neurologic outcome. After severe impact-acceleration-induced injury, blood-free magnesium levels significantly declined (p < 0.05) by 25% and remained depressed for at least 4 days after injury. After moderate injury, the decline in blood-free magnesium was less than that observed in the severe injury group with respect to both degree of decline and duration of decline. The post-traumatic blood-free magnesium concentration correlated to observed motor deficits as assessed by rotarod evaluation (p < 0.001). We conclude that blood-free magnesium levels may be a prognostic indicator of outcome following severe traumatic brain injury.
Animals↗
Neuroprotective effects of MgSO4 and MgCl2 in closed head injury: a comparative phosphorus NMR study.
Previous studies have shown that free magnesium levels decline after traumatic brain injury and that magnesium salt administration improves posttraumatic outcome. These earlier studies, however, have been limited to models of injury that do not produce a significant degree of diffuse axonal injury and have used either MgSO4 or MgCl2 as the magnesium salt. The present study compares the neuroprotective efficacy of MgSO4 and MgCl2 in a severe model of diffuse axonal injury in rats using phosphorus nuclear magnetic resonance spectroscopy and the rotarod test to monitor effects on metabolism and neurologic outcome, respectively. Both MgSO4 and MgCl2 given as a bolus of 100 micromoles/kg at 30 min after severe, closed head injury significantly improved brain intracellular free magnesium concentration and neurologic outcome. These findings suggest that both salts penetrate the blood-brain barrier after brain trauma, enter injured tissue, and subsequently improve neurologic outcome.
Animals↗
Magnesium sulphate improves neurologic outcome following severe closed head injury in rats.
While recent evidence suggests that brain intracellular free magnesium concentration declines following severe diffuse traumatic brain injury, no studies have examined whether magnesium administration following such injury can improve subsequent neurologic outcome. The present study shows that MgSO4 administered as a bolus at 30 min following severe closed head injury in rats significantly improves posttraumatic neurologic outcome as assessed by both rotarod and angleboard tests. Moreover, this improvement in outcome was evident with both intravenous and intramuscular drug administration. We conclude that parenteral administration of magnesium sulphate may be neuroprotective following severe closed head injury of a diffuse nature.
Animals↗
Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS study.
Effects of blood glucose concentration on biochemical and neurologic outcome following lateral fluid percussion-induced traumatic injury of moderate severity (2.8 atm) in rats were studied using radioactive phosphorus (31P) magnetic resonance spectroscopy (MRS) and a battery of tests designed to evaluate posttraumatic neurologic motor function. Prior to injury, male Sprague-Dawley rats (n = 18) were randomly assigned to receive either dextrose, 2 ml 50% (wt/vol), zinc insulin (10 IU/kg) or no treatment, thus dividing the animals into hyperglycemic, hypoglycemic, and normoglycemic groups, respectively. Animals were then injured, monitored for 4 h by 31P MRS before being allowed to recover, and assessed for posttraumatic motor function. Following brain injury, there was no difference in brain intracellular pH between groups over the 4-h posttraumatic MRS monitoring period. Similarly, intracellular free magnesium, cytosolic phosphorylation potential, and neurologic outcome posttrauma were not significantly different between groups. We conclude that, unlike models of ischemia, blood glucose concentration may not be a significant factor affecting outcome in traumatic brain injury.
Animals↗
Traumatic brain axonal injury produces sustained decline in intracellular free magnesium concentration.
Decline in brain intracellular free magnesium concentration following experimental traumatic brain injury has been widely reported in a number of studies. However, to date, these studies have been confined to focal models of brain injury and temporally limited to the immediate 8-h period post-trauma. Recently, a new model of impact-acceleration brain injury has been developed which produces nonfocal diffuse axonal injury more typical of severe clinical trauma. The present study has used phosphorus magnetic resonance spectroscopy and the rotarod motor test to characterise magnesium homeostasis and neurologic outcome over a period of 8 days after induction of severe impact-acceleration injury in rats. Severe impact-acceleration induced injury resulted in a highly significant and sustained decline in intracellular free magnesium concentration that was apparent for 4 days post-trauma with recovery to preinjury levels by day six. There were no significant changes in pH or ATP concentration at any time point post-injury. All animals demonstrated a significant neurologic deficit over the assessment period. The extended period of magnesium decline after severe diffuse brain trauma suggests that repeated administration may be required for pharmacotherapies targeted at restoring magnesium homeostasis.
Animals↗
Acute and prolonged alterations in brain free magnesium following fluid percussion-induced brain trauma in rats.
Several studies have reported declines in brain total and free magnesium concentration after a traumatic insult to the CNS. Although the evidence suggests that this magnesium decline is associated with eventual neurologic outcome after trauma, the duration of free magnesium decline and its impact on related bioenergetic variables are relatively unknown. The present study has therefore used phosphorus magnetic resonance spectroscopy to determine the length of time that free magnesium remains suppressed after traumatic brain injury in rats. Immediately after the traumatic event, brain intracellular free magnesium declined to < 60% of preinjury values and remained significantly depressed (50 +/- 8%; p < 0.001) for 5 days before recovering to preinjury levels by day 8. Cytosolic phosphorylation ratio and mitochondrial oxidative capacity also significantly decreased (p = 0.008) and increased (p = 0.002), respectively, after trauma. However, unlike the time of maximum magnesium change, the maximum changes in these bioenergetic variables occurred at 16-24 h after trauma and thereafter remained stable until after the magnesium had recovered. We conclude that free magnesium decline after trauma precedes changes in bioenergetic variables. Furthermore, therapies targeted at reestablishing magnesium homeostasis after trauma may require administration over a 1-week period.
Animals↗